With the westernization of dietary habit, patients with cancer of the large intestine are increasing in number among Japanese. It is said that cases of colorectal cancer will exceed those of gastric cancer in number in the 21st century, predominating over other malignant tumors along with lung cancer and breast cancer.
Colorectal cancer is treated by surgical resection, which includes endoscopic polypectomy for early colorectal cancer which is an early carcinoma, and abdominoperineal resection of the rectum, abdominosacral resection of the rectum, pull-through operation, low anterior resection, total pelvic exenteration, Hartmann operation and colostomy for progressive cancers. Radical surgery results in a 5-year survival rate of 50 to 60%. The closer the lesion to the rectum, the higher is the rate of recurrence. The site of recurrence is most frequently local. Distant metastases generally occur to the liver and the lung. The rate of such recurrence or metastasis is about 40% for rectal cancer and about 20% for lung cancer. It is empirically known that the recurrence or metastasis is attributable to the presence of a metastasized lesion not detectable macroscopically or to the spread or dissemination of cancer cells by surgical manipulation. Improvements in the oncologic result of large intestinal cancer are dependent not only on early detection but also on how to prevent recurrence or metastasis after surgical resection. For this purpose, it is general practice to conduct adjuvant therapies including (1) chemotherapy, (2) radiotherapy, (3) immunotherapy, (4) thermotherapy, or (5) other treatment. These therapies are performed singly or in combination pre- or post-operatively or during operation. Among these adjuvant therapies, chemotherapy and radiotherapy are widely performed.
Carter summarized 5-fluorouracil (5FU) administration schedules in an introduction to colorectal cancer, including a method wherein a standard loading dose (SLD) of 370 to 500 mg/m.sup.2 bolus (intravenous injection for 5 to 10 min) is given for 5 days, and this dosage regimen is repeated every 4 to 5 weeks. Reportedly, this method achieves effectiveness of 19% (Cancer Treat Rev. 1: 111-129 1974), whereas it is reported that SLD attains effectiveness of 7 to 29% according to research in recent years.
Lokich et al. compared administration of 5FU at a dose of 500 mg/M.sup.2 bolus for 5 days every 5 weeks with CVI (continuous intravenous infusion) of the drug at 300 mg/m.sup.2 /day, reporting that the respective regimens were 7% and 30% in effectiveness, hence a significant difference, but that there was no difference between the resulting survival periods which were 11.2 months and 10.3 months (J. Clin. Oncol. 7: 425-432 1989). Thus, CVI of 5FU over a prolonged period produces an improved effect but still fails to lengthen the survival period.
Various improvements in the dosage regimen of 5FU and research on drugs for use in combination therewith have been made in order to improve such results of treatments. Extensive research has been conducted on therapies comprising CVI of 5FU and use of other anticancer drugs in combination. The drugs to be used in combination with 5FU include Adriamycin, mitomycin C, carmustine, semustine, leucovorin and cisplatin, whereas satisfactory results still remain to be reported.
On the other hand, research has been carried out also on the basis of the therapy comprising CVI of 5FU and use of a multiplicity of drugs in combination with the infusion. Fujii et al. conducted CVI of 5FU in rats implanted with Yoshida sarcoma at a low concentration (20 mg/kg/day) for a prolonged period of time consecutively for 6 days, in combination with oral administration of UFT (to be described later) at a dose of 20 mg/kg once every day, whereby an excellent tumor diminution effect was obtained along with suppressed leukopenia (Jpn. J. Cancer Res. 80, 509-512, 1989).